GENE-TRANSFER INTO HEMATOPOIETIC-CELLS

Transfer of a gene into stem cells with subsequent lineage-specific ge ne expression is a desired goal with many potential therapeutic applic ations. Retroviral vectors developed from murine leukemia viruses repr oducibly transfer genes into murine stem cells, but are inefficient at gene insertion into stem cells of larger animals or man, A growing kn owledge of stem cell biology suggests that this inefficiency reflects the quiescent state of stem cells, even when incubated in the presence of multiple cytokines and low expression of the receptor for amphotro pic retroviral vectors, Alternative vector systems are being explored in an effort to overcome these barriers to stem cell-targeted gene tra nsfer. Our work has shown that recombinant adeno-associated virus vect ors, which have the potential for transducing quiescent cells, transfe r, express and integrate a globin gene linked to its normal regulatory elements in human erythroid cells, but only at very high multipliciti es of infection. The integrated genome was stable and the encoded glob in gene aas expressed at levels equivalent to a normal globin gene.